Topical preparations - suppositories Flashcards
what type of suppositories are available
rectal
vaginal
urethral
define suppositories
suppositories are solid dosage forms intended for insertion into body orifices where they MELT, SOFTEN, OR DISSOLVE and exert localized OR systemic effects
true or false
suppositories are solid dosage forms and only provide systemic effects
false
they are solid dosage forms but can provide local or systemic effects
explain the shape, length, and mass of rectal suppositories
cylindrical shape
~32mm in length
~2 grams* (NO MORE THAN 2 GRAMS)
Explain the shape and mass of vaginal suppositories
pessaries, globular or cone shaped
~5 grams
explain the shape and mass of urethral suppositories
slender, pencil shaped
~4 grams
explain the action of local suppositories
the suppository base melts, softens, or dissolves and delivers the medication to the tissues of that local region
name 4 things in which the local action of suppositories can provide relief
pain
irritation
itching
inflammation
explain what hemorroidal suppositories are.
do they provide local or systemic effects?
local effects
they are local anesthetics, vasoconstrictors, astringents, analgesics, soothing emollients, and protective agents
what can vaginal suppositories be used for
contraceptives and antiseptics
give an example of a vaginal contraceptive and how it works
nonxynol-9
is a surfactant that can interact with the cell membrane and be a barrier
what LOCAL action can urethral suppositories have
antibacterials and local anesthetics
which type of suppositories can be used for systemic effects and why?
rectal and vaginal, because many drugs can be absorbed through the mucous membranes in those areas
name 5 advantages that systemic suppositories have over the oral route
-effective route for patients who have vomiting issues
-convenient route for patients or are unable or unwilling to swallow medication
-bypass hepatic first pass metabolism
-a drug that is irritating to the stomach when given orally can be given via suppository and not cause this irritation
-avoids GI incompatibility of drugs (inactivation of drugs by the pH or enzymatic activity of the stomach)
which have more options available to provide systemic effects – ointments, creams, or suppositories?
suppositories have the most
what is the length of the human rectum
15-30cm
how many mL of insert fluid is available for the human rectum
2-3mL
true or false
there are villi and microvilli present in the human rectum
FALSE – there is not
speak about the vascularization of the human rectum
there is abundant blood vascularization and lymphatic vessels
the lower hemorrhoidal veins that surround the colon receive the absorbed drug and initiate circulation throughout the body, BYPASSING THE LIVER (not 100%)
lymphatic circulation assists in the absorption
true or false
in the case of drug absorption from rectal suppositories, first pass effects are 100% avoided
FALSE
the lower hemorrhoidal veins that surround the colon receive the absorbed drug and initiate circulation throughout the body which bypasses the liver, BUT the upper region of the rectum may absorb some drug as well and go to the hepatic vein
what assists in drug absorption from rectal suppositories
lymphatic circulation
explain the pH and buffer capacity of the human rectum
the pH of the rectal fluid is around 7-8 and has NO buffer capacity
the pH of the human rectum is 7-8 (about neutral)
what is the benefit of this?
don’t have to worry about an acid-base reaction occurring and the drug is generally NOT chemically changed in the rectal environment
explain how colonic contents (contents of the colon) can affect drug absorption through the rectum
a void (empty) rectum provides greater absorption
diarrhea and colonic obstruction due to a tumor will lessen absorption
what physiochemical factors must be considered with drug absorption from the rectum
the lipid-water solubility and the particle size
why is particle size a physiochemical factor to consider when considering drug absorption from rectal suppositories
the partition coefficient
a lipophilic drug in a fatty suppository base at a low concentration will have less tendency to escape from the base and will result in LOW bioavailability because the majority of the drug will remain in the suppositiry
why is particle size a concern when considering the absorption of drugs from rectal suppositories
the smaller the particle size, the more readily available the drug is for absorption
true or false
when considering rectal suppositories, it is not ideal to have the drug be very soluble in the base because the drug won’t release much and bioavailability will be low
TRUE
Classify the suppository bases
-fatty or oleaginous
-water soluble or water miscible
-miscellaneous
explain the ideal suppository base
-bland and non irritating, chemically stable, compatible with the med, easily forms a solid by compressing or molding, remains a solid at room temp but softens, melts, or dissolves readily at body temp
true or false
a strong drug-base interaction inhibits the release of the drug
TRUE
why must a suppository base be capable of melting, softening, or dissolving?
to release the medication
for which are we more concerned with irritation - suppositories or ointments?
suppositories bc the tissues where they’re inserted are very sensitive
what are the most frequently used suppository bases
fatty or oleaginous bases (hydrocarbons)
give 5 examples of fatty/oleaginous suppository bases.
which is the most popular
cocoa butter**
palm kernel oil
cottonseed oil
glyceryl monostearate
glyceryl monopalmitate
explain all of the properties of cocoa butter.
include:
-where is it obtained from
-what color and state of matter
-what chemical structure
-what temp does it melt
-what solidifying agents are included
natural product obtained from Theobroma Cacao
yellowish-white solid
chemically – a triglyceride
melts at 30-36 degrees C
solidfiying agents: cetyl esters wax (beeswax)
true or false
cocoa butter contains water
FALSE - does not contain water. it is a triglyceride that contains fatty acid groups
what is a disadvantage of cocoa butter that sometimes causes us to use PEG instead
it melts at 30-36 degrees celsius which is around our body temperature.
thus, if we hold it for too long it’ll start to get soft
give 5 advantages of PEG bases
-do not need to be formulated to melt at body temp
-its melting point is considerably higher than body temp. convenient for storage – does not need fridge
-PEG bases permit slow release of the drug
-easy to handle when administering
-do not leak from the orifice (like many cocoa butter base suppositories)
name the water-soluble/water miscible suppository bases that are available in the market
glycerinated gelatin and PEG bases (carbowax)
true or false
water soluble/water miscible suppository bases do NOT contain water
TRUE
which is more popular as a water soluble/water miscible suppository base - glycerinated gelatin or PEG bases
PEG is more popular
explain PEG suppository bases (carbowax)
mix PEG 200-600 (clear liquid) with PEG 1000 or more (wax-like, white solid) to get the desired consistency
PEG 200, 400, 600, 1000, 1500, 1540, 3350, 4000, 6000, AND 8000 are used
explain how PEG bases are used and how they are formed
they do not melt at body temp (like cocoa butter), they dissolve slowly in the body fluids. this allows for controlled release for a prolonged period of time/
formed via FUSION METHOD (uses heat)
explain why glycerinated gelatin water soluble/water miscible base contains the ingredients it does
gelatin is also a component of capsules.
glycerin is added to soften the gelatin
true or false
ointment bases cannot be used for suppository bases
false - a lot can
true or false
suppository bases do not contain water
true
explain the difference in storage between cocoa butter and PEG
cocoa butter must be stored in the fridge because it softens at room tmep, but PEG does not
true or false
miscelaneous suppository bases are normally not used
true
name some formulation variables for suppository based
physical state
particle size
solubility
viscosity
brittleness
volume contraction
drug release rates
special problems
what can the physical state of the API of the suppository base be?
can be liquid or powder
of the formulation variables for suppository bases, which are related to the drug itself ?
physical state
particle size
solubility
small particle size = ____solubility and ____ bioavailability
high solubility and high bioavailability
what are some things to consider if the drug used in the suppository are solid particles?
need to use levitation to sufficiently reduce the particle size
what is aspirin solubility in PEG base? what does this mean?
aspirin solubility in PEG base is LOW
therefore, a little of the drug will dissolve in the PEG base and the insoluble particles will be dispersed in the base.
THIS IS HOW THE RELEASE RATE IS CONTROLLED
how is solubility a concern when formulating suppositories
the solubility of the drug in the base used — helps to control the release rate
explain the ideal “brittleness” of the suppository base
it cannot be easily broken. we want to maintain ridgedness to a certain extent but not break it when inserted
explain the release rate of:
oil-soluble drug in an oily base
slow release bc of poor escaping tendency
this will provide long duration
explain the drug release rate of:
water soluble drug in an oily base
this will provide RAPID RELEASE
the solubility is bad so some drug dissolves but not a lot. thus, only a small quantity of drug is needed.
is this acceptable:
solubility of the drug is 10mg in 100g.
solubility of the drug in the base is very bad.
1 mg will provide therapeutic effect
YES it is okay. most of the drug will be able to release out because solubility is so poor
explain the drug release rate of:
oil soluble drug in water muscle base (PEG)
MODERATE RELEASE
explain the drug release rate of:
water miscible drug in water miscible base
moderate release — all based on diffusion
all are water soluble
true or false
when a drug dissolves in the suppository base, it can easily escape to provide therapeutic effect
FALSE
the drug will remain there and not come out
the INSOLUBLE PARTICLES are the ones that are able to escape
true or false
suppositories can only contain solid/powder API
false
can contain liquid API as welll
how is “volume contraction” a formulation consideration when preparing suppositories?
in the molding method, when the suppository is placed in the fridge some of the material changes
the amount that changed depends on the drug and how much base we use
true or false
for both suppositories and ointments, the amount of drug incorporated is usually low
true
true or false
drug release rates only apply to suppositories
FALSE
applies to ointments and suppositories
how many methods are there for preparation of suppositories? name them
3:
molding
hand rolling and shaping
compression
explain the molding method of preparing suppositories
the base is melted. the melt is incorporated into the molds. allow the melt to cool and congeal (harden) into suppositories. remove the formed suppositories from the mold
the mold must be lubricated to prevent sticking, and calibrated
determining the amount of base required is challenging
preparing and pouring the melt
name a lubricant for suppository molds
liquid petrolatum (mineral oil)
if you use a HIGH DENSITY DRUG, the volume occupied will be _____
what does this say about the amount of base needed
LOW
therefore, a lot of base will be needed
which suppository base(s) can use hand rolling/shaping as a method of preparation?
ONLY for cocoa butter - not PEG. PEG is not soft enough to be able to do this and needs to be melted
what 2 ingredients require the use of a lubricant in the molding method?
glycerin and gelatin
which suppository base has the more significant volume constriction problem ?
PEG
when it shrinks, it won’t stick to the mold
the compression method of preparing suppositories is mainly used where?
in manufacturing
explain the compression method of preparing suppositories.
where is it mainly used?
prepared by forcing the mixed mass of the suppository based and medicaments into special molds using suppository making machines
suppository base + medicaments + other ingredients undergo thorough mixing prior to this compression
THE COMPRESSION PROCESS IS SUITABLE FOR WHAT KIND OF COMPONENTS
-heat labile (sensitive)
-suppositories containing a great deal of insoluble substances in the base
what suppository bases are suitable for the molding method
cocoa butter
glycerinated gelatin
PEG
most other bases too
true or false
basically any suppository base can use the molding method
TRUE
what kind of components/bases are suitable for the compression method of preparing suppositories ?
heat sensitive components and suppositories containing a lot of insoluble substances
true or false
hand rolling/shaping CANNOT be used for cocoa butter bases
FALSE
can be used for cocoa butter but not PEG because it isn’t soft enough
name 3 stability concerns for suppositories
physical stability
chemical stability
microbiological stability
explain microbiological stability for suppositories
-for COMPOUNDED suppositories - beyond use dating
-for MANUFACTURED suppositories - expiration dating
-inform and education the patient about storage - if PEG, room temp is fine. cocoa butter needs fridge.
glycerin has evaporating issue — needs to be stored properly otherwise it will become brittle when evaporates
explain how a suppository should be inserted
-position patient on left side with upper leg flexed. lubricate the suppository with a water soluble lubricant (or small amount water) if needed.
gently insert suppository a finger length deep at an angle towards umbilicus so the suppository is placed against the rectal wall for ABSORPTION, rather than being left in the canal or pushed into mass of stool
after the finger is withdrawn, hold buttocks together until urge to expel has ceased
low particle size = _____ sedimentation
slow
low viscosity of the suspension = _____ sedimentation
high
true or false
the addition of a flocculating agent will increase the sedimentation rate
true
true or false
increasing the particle size of the active ingredient will decrease sedimentation rate
false - increase
true or false
particles in flocculated suspensions exist as separate entities
FALSE - deflocculated
is the sedimentation rate high in flocculated or deflocculated suspensions?
flocculated
true or false
talc can be used as a suspending agent
false
name 2 suspending agents
acacia
methylcellulose
name 2 advantages of aerosol dosage forms
fine particle size
less contamination
true or false
aerosol dosage forms are relatively inexpensive to make
false - expensive
propellants used in aerosols have ___ vapor pressure at 70 degrees fahrenheit
high
what does high vapor pressure mean
they easily evaporate
true or false
propellants used in aerosols may not dissolve in water
TRUE
true or false
the propellants used in aerosols have liquid densities LOWER than water at 70 degrees fahrenheit
true
substances used as suppository bases that DISSOLVE rather than melt…
any PEG
true or false
water soluble bases do not contain aqueous solution
TRUE
true or false
absorption bases contain aqueous solution
true — when anhydrous becomes W/O emulsions
true or false
hydrocarbon bases can be used for preparation of W/O emulsions
false
true or false
absorption bases can be used for preparation of W/O emulsions
true
true or false
water removable bases can be used for preparation of W/O emulsions
FALSE
can an aqueous solution be incorporated into white petrolatum?
no - it is hydrocarbon base
can aqueous solution be incorporated into vaseline?
NO - hydrocarbon
true or false
lanolin can be used to incorporate aqueous solutions
yes — it is an absorption base
nitroglycerin TDDS can be compared on the basis of?
the number of mg of nitroglycerin delivered in 24 hours
daily delivery amount
true or false
Nitro-Dur contains nicotine
false - nitroglycerin
name some penetration enhancers for TDDS
DMS (decylmethylsulfoxide)
oleic acid
azone
alcohol
are pseudoplastic flow and thixotropic flow desirable properties in pharmaceutical suspensions?
yes
explain a Dilatant
a liquid who’s viscosity is increased when stress is applied
as you agitate, viscosity increases
in which type of flow are substances called “shear thinning” systems
pseduoplastic flow
“the flow curve begins at the origin and there is no yield value””
pseudoplastic flow
true or false
for pseudoplastic flow, the viscosity of the substances increases with increasing shear rate
FALSE
